Administering of active components into the human body requires the use of an appropriate vehicle for bringing an effective amount of the active component intact to the desired site in the human body. The desired site varies and it may be the blood stream, organs, cells etc. Active components that dissolve very poorly in oil or water pose a problem as to the route for their administration, transport and reaching their target. Furthermore, many chemicals that can serve as appropriate vehicles for such active compounds cannot be used in association with the human body, i.e. their use is unsafe or even hazardous. Constructing the appropriate vehicle and the desired efficient formulation, poses a challenge to developers of new medicaments.
Nutraceuticals, which are food supplements with health benefits, are commonly used as part of the daily diet. Nutraceuticals are vitamins, minerals, extracts of natural components (for example plants, flowers, roots or leaves), which are not medicaments, yet are believed to have a positive effect on the human body. They may have a long-term effect or an immediate effect and may be used for long treatment of chronic, yet not terminal diseases.
Nutraceuticals may be used for example in order to lower blood pressure, reduce cancer risk factors, regulate the digestive tract system, strengthen immune systems, regulate growth, regulate sugar concentration in blood, lower cholesterol levels, serve as antioxidant agents and more. Antioxidants can donate electrons to quench and neutralize free radical oxygen molecules, which play an important role in the initiation and promotion of atherosclerosis, cancer, cataract, arthritis and other degenerative diseases. Antioxidants can be (i) water-soluble such as vitamin C, simple phenois, polyphenois, bioflavonoids, rosmarinic acid, catechins, or (ii) oil-soluble (lipophilic) such as vitamin E, C0–Q10 (coenzyme Q10, ubiquinone), vitamin D, vitamin B12, carotenoids (lycopene, β-carotene, lutein), etc.
Examples of health benefits of some Nutraceuticals are: (i) Lycopene may protect against coronary vascular disease, reduce risk factors of prostate cancer, shrink tumors and reduce risk of upper digestive tract cancers. (ii) Lutein, in addition to its antioxidant activity, reduces the incidence of cataract limits blue light damage and reduces age-related macular degeneration and (iii) Phytosterols are used for reducing cholesterol adsorption.
Although the use of nutraceuticals in capsules and tablets is abundant, their effect is frequently diminished or even lost since many of the nutraceuticals are not soluble in water, vegetable oils or food-grade solvents. Due to their low solubility, they cannot penetrate into the mete therefore their bioavailability is very poor.
A common approach for constructing an appropriate vehicle for transporting nutraceuticals, medicaments, peptides or proteins is the use of microemulsions. In the microemulsion, the active compounds are not soluble but rather are solubilized. The general concept of solubilization of active components and its utilization may be found in the following review articles: 1. Solans, C., Pons, R., Kunieda, H “Overview of basic aspects of microemulsions” Industrial Applications of Microemulsions, Solans, C., Kunieda, H. Eds.; Dekker: New York, (1997); 66:1-17; 2 Dungan, S. R. “Microemulsions in foods: properties and applications” ibid 148–170; 3. Holmberg, K. “Quarter century progress and new horizons in microemulsions” in Micelles, Microemulsions and Monolayers, Shah, 0. Ed.; Dekker: New York (1998) 161–192; 4. Garti, N., “Microemulsions, emulsions, double emulsions and emulsions in food” in Formulation Science (proceeding from formulation forum '97-association of formulation chemists) (1998) 1, 147–219; 5. Ezrahi, S., Aserin, A., Garti, N. in Microemulsions-fundamental wad applied aspects Kumar, P. and Mittal, K. L. Eds. Marcel Dekker, Inc. New York (1999) “Aggregation behavior in one-phase (Winsor IV) systems” 185–246; 6. Garti, N., Clement, V., Leser, M., Aserin, A. Fanun, M. “Sucrose esters microemulsions J. Molec. Liquids (1999) 80, 253–296.
U.S. Pat. No. 6,063,762 describes a microemulsion for cyclosporin, consisting of oil, surfactant and a lipophilic solvent comprising of an ester of polycarboxylic acid and/or carboxylic acid ester of polyols. GB 588,298 describes a system for solubilizing lipoid soluble vitamins, comprising of polyalkylene oxide derivative of a partial fatty acid (more than C12) and an ester of polyhydric alcohol, where the resulting solution is miscible in water or aqueous solutions. U.S. Pat. No. 5,725,803 discloses a new emulsifier for a water/oil system, comprising of phytosterol, 5–23 wt % C20-24-alkyl alcohol and a mixture of C10-28-fatty alcohols. WO 99/53,925 describes a composition comprising of phytosterols and lecithin which is dispersed in water by shaking, vortexing, sonicating or passing through a small orifice. WO 99/39,715 describes yet another system for solubilizing phytosterols by macromolecules, such as starch or saccharides.
Ultramicroemulsions and their use in pharmaceutical preparations are described in U.S. Pat. No. 6,057,359 as an aqueous ultramicroemulsion, in U.S. Pat. No. 5,536,504 for ultramicroemulsions containing xanthophyll esters, in U.S. Pat. No. 6,180,661 where flavanol-glycoside per-esters are used for achieving an ultramicroemulsion, and in U.S. Pat. No. 6,248,363.